%0 Journal Article %1 Cantuti-Castelvetri2020.06.07.137802 %A Cantuti-Castelvetri, Ludovico %A Ojha, Ravi %A Pedro, Liliana D. %A Djannatian, Minou %A Franz, Jonas %A Kuivanen, Suvi %A Kallio, Katri %A Kaya, Tugberk %A Anastasina, Maria %A Smura, Teemu %A Levanov, Lev %A Szirovicza, Leonora %A Tobi, Allan %A Kallio-Kokko, Hannimari %A Österlund, Pamela %A Joensuu, Merja %A Meunier, Frédéric A. %A Butcher, Sarah %A Winkler, Martin Sebastian %A Mollenhauer, Brit %A Helenius, Ari %A Gokce, Ozgun %A Teesalu, Tambet %A Hepojoki, Jussi %A Vapalahti, Olli %A Stadelmann, Christine %A Balistreri, Giuseppe %A Simons, Mikael %D 2020 %I Cold Spring Harbor Laboratory %J bioRxiv %K ace2 covid-19 nrp1 %R 10.1101/2020.06.07.137802 %T Neuropilin-1 facilitates SARS-CoV-2 cell entry and provides a possible pathway into the central nervous system %U https://www.biorxiv.org/content/early/2020/06/07/2020.06.07.137802 %X The causative agent of the current pandemic and coronavirus disease 2019 (COVID-19) is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)1. Understanding how SARS-CoV-2 enters and spreads within human organs is crucial for developing strategies to prevent viral dissemination. For many viruses, tissue tropism is determined by the availability of virus receptors on the surface of host cells2. Both SARS-CoV and SARS-CoV-2 use angiotensin-converting enzyme 2 (ACE2) as a host receptor, yet, their tropisms differ3-5. Here, we found that the cellular receptor neuropilin-1 (NRP1), known to bind furin-cleaved substrates, significantly potentiates SARS-CoV-2 infectivity, which was inhibited by a monoclonal blocking antibody against the extracellular b1b2 domain of NRP1. NRP1 is abundantly expressed in the respiratory and olfactory epithelium, with highest expression in endothelial cells and in the epithelial cells facing the nasal cavity. Neuropathological analysis of human COVID-19 autopsies revealed SARS-CoV-2 infected NRP1-positive cells in the olfactory epithelium and bulb. In the olfactory bulb infection was detected particularly within NRP1-positive endothelial cells of small capillaries and medium-sized vessels. Studies in mice demonstrated, after intranasal application, NRP1-mediated transport of virus-sized particles into the central nervous system. Thus, NRP1 could explain the enhanced tropism and spreading of SARS-CoV-2.Competing Interest StatementThe authors have declared no competing interest.

@article{Cantuti-Castelvetri2020.06.07.137802, abstract = {The causative agent of the current pandemic and coronavirus disease 2019 (COVID-19) is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)1. Understanding how SARS-CoV-2 enters and spreads within human organs is crucial for developing strategies to prevent viral dissemination. For many viruses, tissue tropism is determined by the availability of virus receptors on the surface of host cells2. Both SARS-CoV and SARS-CoV-2 use angiotensin-converting enzyme 2 (ACE2) as a host receptor, yet, their tropisms differ3-5. Here, we found that the cellular receptor neuropilin-1 (NRP1), known to bind furin-cleaved substrates, significantly potentiates SARS-CoV-2 infectivity, which was inhibited by a monoclonal blocking antibody against the extracellular b1b2 domain of NRP1. NRP1 is abundantly expressed in the respiratory and olfactory epithelium, with highest expression in endothelial cells and in the epithelial cells facing the nasal cavity. Neuropathological analysis of human COVID-19 autopsies revealed SARS-CoV-2 infected NRP1-positive cells in the olfactory epithelium and bulb. In the olfactory bulb infection was detected particularly within NRP1-positive endothelial cells of small capillaries and medium-sized vessels. Studies in mice demonstrated, after intranasal application, NRP1-mediated transport of virus-sized particles into the central nervous system. Thus, NRP1 could explain the enhanced tropism and spreading of SARS-CoV-2.Competing Interest StatementThe authors have declared no competing interest.}, added-at = {2020-06-14T12:45:30.000+0200}, author = {Cantuti-Castelvetri, Ludovico and Ojha, Ravi and Pedro, Liliana D. and Djannatian, Minou and Franz, Jonas and Kuivanen, Suvi and Kallio, Katri and Kaya, Tu{\u g}berk and Anastasina, Maria and Smura, Teemu and Levanov, Lev and Szirovicza, Leonora and Tobi, Allan and Kallio-Kokko, Hannimari and {\"O}sterlund, Pamela and Joensuu, Merja and Meunier, Fr{\'e}d{\'e}ric A. and Butcher, Sarah and Winkler, Martin Sebastian and Mollenhauer, Brit and Helenius, Ari and Gokce, Ozgun and Teesalu, Tambet and Hepojoki, Jussi and Vapalahti, Olli and Stadelmann, Christine and Balistreri, Giuseppe and Simons, Mikael}, biburl = {https://www.bibsonomy.org/bibtex/248c101d4812690bd4681510eb9629f2d/fordham1}, description = {Neuropilin-1 facilitates SARS-CoV-2 cell entry and provides a possible pathway into the central nervous system | bioRxiv}, doi = {10.1101/2020.06.07.137802}, elocation-id = {2020.06.07.137802}, eprint = {https://www.biorxiv.org/content/early/2020/06/07/2020.06.07.137802.full.pdf}, interhash = {3ff90bb49e9ebb4f352c18cdbb488d1d}, intrahash = {48c101d4812690bd4681510eb9629f2d}, journal = {bioRxiv}, keywords = {ace2 covid-19 nrp1}, publisher = {Cold Spring Harbor Laboratory}, timestamp = {2020-06-14T12:45:30.000+0200}, title = {Neuropilin-1 facilitates SARS-CoV-2 cell entry and provides a possible pathway into the central nervous system}, url = {https://www.biorxiv.org/content/early/2020/06/07/2020.06.07.137802}, year = 2020 }